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Mussap M.,Italian National Cancer Institute | Noto A.,Puericulture Institute and Neonatal Section | Fanos V.,Puericulture Institute and Neonatal Section | Fanos V.,University of Cagliari
Clinica Chimica Acta | Year: 2013

Metabolomics consists of the quantitative analysis of a large number of low molecular mass metabolites involving substrates or products in metabolic pathways existing in all living systems. The analysis of the metabolic profile detectable in a human biological fluid allows to instantly identify changes in the composition of endogenous and exogenous metabolites caused by the interaction between specific physiopathological states, gene expression, and environment. In pediatrics and neonatology, metabolomics offers new encouraging perspectives for the improvement of critically ill patient outcome, for the early recognition of metabolic profiles associated with the development of diseases in the adult life, and for delivery of individualized medicine. In this view, nutrimetabolomics, based on the recognition of specific cluster of metabolites associated with nutrition and pharmacometabolomics, based on the capacity to personalize drug therapy by analyzing metabolic modifications due to therapeutic treatment may open new frontiers in the prevention and in the treatment of pediatric and neonatal diseases. This review summarizes the most relevant results published in the literature on the application of metabolomics in pediatric and neonatal clinical settings. However, there is the urgent need to standardize physiological and preanalytical variables, analytical methods, data processing, and result presentation, before establishing the definitive clinical value of results. © 2013 Elsevier B.V.

Mussap M.,Italian National Cancer Institute | Noto A.,Puericulture Institute and Neonatal Section | Cibecchini F.,Italian National Cancer Institute | Fanos V.,Puericulture Institute and Neonatal Section
Seminars in Fetal and Neonatal Medicine | Year: 2013

Despite a 35% decline in the mortality rate for infants aged <5 years over the past two decades, every year nearly 40% of all deaths in this age group occur in the neonatal period, defined as the first 28 days of life. New knowledge on molecular and biochemical pathways in neonatal diseases will lead to the discovery of new candidate biomarkers potentially useful in clinical practice. In the era of personalized medicine, biomarkers may play a strategic role in accelerating the decline in neonatal mortality by assessing the risk of developing neonatal diseases, by implementing tailored therapeutic treatment, and by predicting the clinical outcome. However, there is an urgent need to reduce the gap in translating newly acquired knowledge from bench to bedside. Traditional and candidate biomarkers for neonatal sepsis and necrotizing enterocolitis will be discussed in this review, such as C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA), soluble form of CD14 subtype presepsin (sCD14-ST), lipolysaccharide binding protein (LBP), angiopoietins (Ang)-1 and -2, soluble form of triggering receptor expressed on myeloid cells (sTREM-1), soluble form of urokinase-type plasminogen activator receptor (suPAR), platelet-activating factor (PAF) and calprotectin. New frontiers in managing critically ill newborns may be opened by metabolomics, a diagnostic tool based on the recognition of metabolites contained in biological fluids. Metabolomics represents the passage from a descriptive science to a predictive science, having the potential to translate benchtop research to real clinical benefits. © 2012 Elsevier Ltd.

Dessi A.,Puericulture Institute and Neonatal Section | Ottonello G.,Puericulture Institute and Neonatal Section | Fanos V.,Puericulture Institute and Neonatal Section | Fanos V.,University of Cagliari
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2012

It is well know that adverse conditions during intrauterine life, such as intrauterine growth restriction (IUGR), can result in permanent changes in the physiology and metabolism of the newborn, which in turn leads to an increased risk of disease in adulthood (fetal origin of adult disease hypothesis). In the first part of this review the epidemiological studies in which a correlation between low birth weight and chronic pathologies in adulthood was observed are reported. The second part of the review is focused on metabolomics studies that have revealed an altered metabolism in IUGR patients compared to controls. Together with more classic biomarkers of IUGR, such as endothelin-1, leptin, protein S100B and visfatin, the new holistic metabolomics approach has assumed a crescent role in the identification of disorders in the neonatal metabolic profile, determined by the interconnection of the different processes. © 2012 Informa UK, Ltd.

Fanos V.,Puericulture Institute and Neonatal Section | Fanos V.,University of Cagliari | Fanni C.,Puericulture Institute and Neonatal Section | Ottonello G.,Puericulture Institute and Neonatal Section | And 3 more authors.
Molecules | Year: 2013

Metabolomics, the latest of the "omics" sciences, has a non-selective approach and can thus lead to the identification of all the metabolites (molecules < 1 kDa) in a biological system. The metabolomic profile can be considered the most predictive phenotype capable of evaluating epigenetic modifications determined by external factors. It is so close to the phenotype as to be considered the phenotype itself in its unique individuality (fingerprinting), both in health (phenome), and disease (diseasome). Urine, compared to other biological liquids, has the advantage of being a complex fluid with many components, including intermediate metabolites. Metabolomics may thus play a role in the study of different kidney diseases and overcome diagnostic difficulties. We shall present the studies that to our knowledge have been published on Nephrology and Pediatric Nephrology. Some are experimental while others are clinical. We have not considered carcinomas and transplantations. Although scarce, the data on adults and the very few ones in pediatrics are quite interesting. Further studies on kidneys are needed to determine the practical clinical impact of metabolomics in kidney renal pathologies. The "multiplatform" "omic" study of urine and namely metabolomics can contribute to improving early diagnosis and the outcome of kidney diseases. © 1996-2013 MDPI AG (Basel, Switzerland).

Mussap M.,Italian National Cancer Institute | Puxeddu E.,Puericulture Institute and Neonatal Section | Puddu M.,Puericulture Institute and Neonatal Section | Ottonello G.,Puericulture Institute and Neonatal Section | And 5 more authors.
Clinica Chimica Acta | Year: 2015

Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3. days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p < 0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p < 0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p = 0.730). In our population, CRP and sCD14-ST did not correlate with each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95% C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7 ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS. © 2015 Elsevier B.V.

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